|
For 50 years scientists have been unsure how the bacteria thatgives humans cholera manages to resist one of our basic innate immune responses. Thatmystery has now been solved, thanks to research from biologists atThe University of Texas at Austin. The answers may help clear the way for a new class of antibiotics that don't directly shut down pathogenic bacteria such as V.cholerae, but instead disable their defenses so that our own immunesystems can do the killing. Every year cholera afflicts millions of people and kills hundredsof thousands, predominantly in the developing world. The infectioncauses profuse diarrhea and vomiting. Death comes from severe dehydration . "If you understand the mechanism, the bacterial target, you're morelikely to be able to design an effective antibiotic," says StephenTrent, associate professor of molecular genetics and microbiologyand lead researcher on the study. The bacterium's defense, which was unmasked this month in theProceedings of the National Academy of Sciences, involves attachingone or two small amino acids to the large molecules, known asendotoxins, that cover about 75 percent of the bacterium's outersurface. "It's like it's hardening its armor so that our defenses can't getthrough," says Trent. Trent says these tiny amino acids simply change the electricalcharge on that outer surface of the bacteria. It goes from negativeto neutral. That's important because the molecules we rely on to fight off suchbacteria, which are called cationic antimicrobial peptides (CAMPs),are positively charged. They can bind to the negatively chargedsurface of bacteria, and when they do so, they insert themselvesinto the bacterial membrane and form a pore. Water then flowsthrough the pore into the bacterium and pops it open from theinside, killing the harmful bacteria. It's an effective defense, which is why these CAMPs are ubiquitousin nature (as well as one of the main ingredients inover-the-counter antibacterial ointments such as Neosporin). However, when the positively charged CAMPs come up against theneutral V. cholerae bacteria, they can't bind. They bounce away,and we're left vulnerable. V. cholerae can then invade our intestines and turn them into akind of factory for producing more cholera, in the processrendering us incapable of holding onto fluids or extractingsufficient nutrients from what we eat and drink. "It pretty much takes over your normal flora," says Trent. Trent says that scientists have known for some time that the strainof V. cholerae responsible for the current pandemic in Haiti andelsewhere is resistant to these CAMPs. It's that resistance that islikely responsible, in part, for why the current strain displacedthe strain that was responsible for previous pandemics. "It's orders of magnitude more resistant," says Trent. Now that Trent and his colleagues understand the mechanism behindthis resistance, they hope to use that knowledge to help developantibiotics that can disable the defense, perhaps by preventing thecholera bacteria from hardening their armor. If that happened, ourCAMPs could do the rest of the work. Trent says the benefits of such an antibiotic would beconsiderable. It might be effective against not just cholera but arange of dangerous bacteria that use similar defenses. And becauseit disarms but doesn't kill the bacteria outright, as traditionalantibiotics do, it might take longer for the bacteria to mutate andevolve resistance in response to it. "If we can go directly at these amino acids that it uses to protectagainst us, and then allow our own innate immune system to kill thebug, there could be less selection pressure," he says. Trent's lab is now screening for compounds that would do preciselythat. Additional References Citations. The e-commerce company in China offers quality products such as Rfid Wrist Band Manufacturer , Rfid Card Reader Manufacturer, and more. For more , please visit Rfid Reader Module today!
Related Articles -
Rfid Wrist Band Manufacturer, Rfid Card Reader Manufacturer,
|
